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PLoS One. 2014 Mar 14;9(3):e91816. doi: 10.1371/journal.pone.0091816. eCollection 2014.

Autoantibodies to agrin in myasthenia gravis patients.

Author information

1
Department of Neuroscience and Regenerative Medicine and Department of Neurology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia, United States of America; Department of Physiology, Basic Medical School, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei Province, P. R. China.
2
Department of Neuroscience and Regenerative Medicine and Department of Neurology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia, United States of America; Charlie Norwood VA Medical Center, Augusta, Georgia, United States of America.
3
Department of Neurology, School of Medicine, Wayne State University, Detroit, Michigan, United States of America.
4
Department of Neurology, School of Medicine, Wayne State University, Detroit, Michigan, United States of America; Department of Biomedical Sciences, Oakland University William Beaumont School of Medicine, Rochester, Michigan, United States of America.
5
Department of Neurology, School of Medicine, Wayne State University, Detroit, Michigan, United States of America; Department of Neurology, Cedars-Sinai Medical Center, West Hollywood, California, United States of America.
6
Department of Neurology, School of Medicine, Wayne State University, Detroit, Michigan, United States of America; Department of Immunology and Microbiology, School of Medicine, Wayne State University, Detroit, Michigan, United States of America.

Abstract

To determine if patients with myasthenia gravis (MG) have antibodies to agrin, a proteoglycan released by motor neurons and is critical for neuromuscular junction (NMJ) formation, we collected serum samples from 93 patients with MG with known status of antibodies to acetylcholine receptor (AChR), muscle specific kinase (MuSK) and lipoprotein-related 4 (LRP4) and samples from control subjects (healthy individuals and individuals with other diseases). Sera were assayed for antibodies to agrin. We found antibodies to agrin in 7 serum samples of MG patients. None of the 25 healthy controls and none of the 55 control neurological patients had agrin antibodies. Two of the four triple negative MG patients (i.e., no detectable AChR, MuSK or LRP4 antibodies, AChR-/MuSK-/LRP4-) had antibodies against agrin. In addition, agrin antibodies were detected in 5 out of 83 AChR+/MuSK-/LRP4- patients but were not found in the 6 patients with MuSK antibodies (AChR-/MuSK+/LRP4-). Sera from MG patients with agrin antibodies were able to recognize recombinant agrin in conditioned media and in transfected HEK293 cells. These sera also inhibited the agrin-induced MuSK phosphorylation and AChR clustering in muscle cells. Together, these observations indicate that agrin is another autoantigen in patients with MG and agrin autoantibodies may be pathogenic through inhibition of agrin/LRP4/MuSK signaling at the NMJ.

PMID:
24632822
PMCID:
PMC3954737
DOI:
10.1371/journal.pone.0091816
[Indexed for MEDLINE]
Free PMC Article
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